Program Director/Principal Investigator (Robey, Ellen, A): Summary: T cells orchestrate immune responses, and defects in T cell development in the thymus can lead to auto- immunity or immunodeficiency. We have developed new methods to directly visualize and manipulate the pattern of TCR signaling during T cell development in living thymic tissue. By examining the impact of these manipulations on T cell development, we expect to gain insights into the mechanistic connections between TCR signaling, thymocyte migration, and different forms of T cell selection. Such information is key to developing improved treatments for a variety of immune system related diseases and to improving our ability to manipulate immune response to tumors or pathogens. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) 2 Page Continuation Format Page